1. Field of the Invention
The invention generally relates to the fields of medicinal and synthetic chemistry. More specifically, the invention relates to the synthesis and use of carotenoid analogs or derivatives.
2. Description of the Relevant Art
Recent studies have demonstrated that initiation of lipid peroxidation and formation of bioactive eicosanoids are critical processes occurring in inflammation, particularly in both atherosclerosis and asthma (reactive airways disease; Zhang et al. 2002; Spanbroek et al. 2003; Dwyer et al. 2004; Helgadottir et al. 2004 are each incorporated herein). The current state of knowledge suggests that lipoxygenases, cyclooxygenases, and cytochrome P450 monooxygenases (CYPs) are the primary enzymatic participants in these lipid peroxidation events (Spector et al. 1988 (incorporated herein); Zhang et al. 2002). In addition, myeloperoxidase (MPO), a heme protein secreted by activated leukocytes, can also generate reactive intermediates that promote lipid peroxidation in vitro and in vivo (Baldus et al. 2003; Brennan et al. 2003 which are each incorporated herein).
In addition to their potent bronchoconstrictor properties, leukotrienes and other products of the 5-lipoxygenase pathway induce pathophysiologic responses similar to those associated with asthma. Specifically, 5-lipoxygenase products can cause tissue edema and migration of eosinophils and can stimulate airway secretions. The leukotrienes also stimulate cell cycling and proliferation of both smooth muscle and various hematopoietic cells; these observations provide further evidence of a potential role of leukotriene modifiers in altering the biology of the airway wall in asthma. Since all these responses contribute to asthma, the pharmaceutical industry initiated research programs to identify substances that could inhibit the action or synthesis of the leukotrienes.
Inhibition of 5-LO pathway activity in vivo will likely find application in those anti-inflammatory applications (e.g. atherosclerosis, asthma) for which downstream mediators of 5-LO activity (e.g. leukotriene B4 or LTB4) are involved in the pathogenesis of disease.